The therapeutic efficacy of pharmaceutical agents is oftentimes diminished as a result of their inadequate solubilities at physiological pH. In addition, the ability to administer some pharmaceutical agents in aqueous solution—for example, via intraperitoneal (I.P.) injection, intramuscular (I.M.) injection, intravenous (I.V.) injection, and the like—is oftentimes not practicable due to the inadequate solubilities of the pharmaceutical agents at the requisite concentrations and/or pH.
As a consequence of such inadequate solubilities, it is oftentimes necessary to restrict the formulation of pharmaceutical agents to peroral dosage forms. However, when oral administration is not feasible, practical or otherwise desirable (e.g., in the treatment of patients who are unable to swallow—such as neonates—as well as critically ill, paralyzed, and/or comatose patients), the inability to administer the pharmaceutical agent in a parenteral dosage form is an acute problem.
A further limitation on the parenteral administration of pharmaceutical agents is observed in connection with compounds having high pKa values. Since pharmaceutical agents having high pKa values typically form solutions with pH values that are above the level at which one could safely or conveniently administer the drug, parenteral administration of such pharmaceutical agent is oftentimes not an option. Indeed, there are presently very few options available for formulating solutions of pharmaceutical agents with high pKa values.
In short, it would be highly desirable to (a) enhance the aqueous solubilities of poorly soluble pharmaceutical agents in order to increase their utilities or availabilities at physiological pH, and/or to (b) buffer the acidities of pharmaceutical agents to acceptable physiological levels without compromising their therapeutic efficacies.